The present invention relates to a process for the production of rosmarinic acid of the formula ##STR2## by enzymatic reaction of 3-(3,4-dihydroxyphenyl)-lactic acid with caffeoyl-coenzyme A in the presence of rosmarinic acid synthase.
The esters of nuclear-substituted cinnamic acids and nuclear-substituted phenyllactic acids have anti-inflammatory properties. Rosmarinic acid (RA), the ester from caffeic acid and the R(+)form of 3-(3,4-dihydroxyphenyl)-lactic acid, was obtained as a naturally occurring substance for the first time from the medicinal plant Rosmarinus officinalis. It has been the subject of intensive research for some years as a potential anti-inflammatory agent. RA has previously been, obtained either from plants or from plant cell cultures.
It has recently been found that cell cultures of Coleus blumei produce rosmarinic acid in considerable quantities. On extraction of the cell mass, M. Petersen and A.W. Alfermann (Z. Naturforsch. 43 c: 501-504 (1988)) isolated two enzymes and identified them based on their activity. A rosmarinic acid synthase was identified as the decisive enzyme for rosmarinic acid synthesis from caffeoyl-CoA and 3-(3,4-dihydroxyphenyl)-lactic acid. Dihydroxyphenylpyruvate reductase, with which the reduction of the keto acid to give the hydroxy acid is achieved in the presence of NADH, was also identified.